Back on May 13th I wrote a post entitled “Evolutionary biology takes a hard look at IVF and human conception”. In it I suggested that aneuploidy – chromosomal abnormality – was in fact normal for human embryos and had evolved as a male strategy for invasiveness in the face of female counter-measures that encapsulated implanting embryos and inspected them for quality and/or compatibility before either accepting or rejecting them. I observed that although fertility failure in human reproduction is very high at about 70%, it is much lower than the amount of chromosomally-abnormal embryos which is in excess of 90%. The obvious conclusion is that some genetically abnormal embryos can go on to make perfectly normal babies.
This sets up the obvious question. How do abnormal embryos “right themselves”? How do they correct these genetic mistakes, or purge them from the developing embryo, once they have neatly side-stepped a mother’s defenses? I suggested that the answer might lie in recent research by Magdalena Zernicka-Goetz of the Gordon Institute in Cambridge, UK, who discovered, thanks to chorionic villus sampling, that 25% of the cells in the placenta of a baby she was incubating at the age of 44 contained aneuploidies. Thankfully her baby was born completely normal. But this motivated Zernicka-Goetz to research the question of why the placenta could be riddled with genetic abnormality but the baby preserved from it. Research with mice embryos made mosaic for aneuploid and normal cells suggested that intense clonal competition among the blastocyst cells that went on to make the baby eradicated all cells that were genetically abnormal, whereas that clonal competition in the fraction of cells that went on to form the placenta was relaxed – allowing clones of aneuploid cells to survive. I suggested to Zernicka-Goetz that this could be an evolved mechanism to retain aneuploidy in the placenta in order to imbue it with the same degree of invasiveness that aneuploidy had already bestowed on the early embryo.
A paper in the journal Reproductive Biology and Endocrinology last week documents five cases of healthy live births of babies formed from aneuploid embryos and questions the necessity for, and effectiveness of, pre-implantation genetic screening, which has been widely adopted by IVF clinics in an attempt to identify aneuploidy in embryos and thus weed out “unviable” embryos. The paper argues that PGS should be abandoned because it may do more harm than good because it produces too many false positives which leads to over-rejection of embryos that could have gone on to make perfectly fine babies. A classic case of iatrogenic medicine that might be adding to the patients’ infertility, not curing it. If so, although these authors do not invoke evolutionary mechanisms explicitly, this story might endure as a prime example of where evolutionary medicine can make a real contribution to medical practice by fundamentally questioning assumptions. The search for the perfect embryo may very well be over.
Deleterious genes for a number of life-threatening diseases which palpably affect human fitness appear to persist in the gene pool at perplexingly high frequencies when you would think they would be eradicated over time by purifying natural selection. Now a group of scientists headed by Tobias Lenz of Harvard Med School and the Max Planck Institute for Evolutionary Biology have come up with the likely answer and it involves an evolutionary trade-off with the process that gives our immune systems the variability they need to counteract the many infectious diseases our environments throw at us. There is an easy-to-read precise of the work by Joseph Caspermeyer, in MBE.
In one part of their study Lenz and his colleagues examined over 160 genes in the MHC – the major histocompatibility complex – which is the area of the human genome that accounts for the cell surface molecules on our adaptive immune cells that recognise the antigens present on germs and guide those cells to attack them. Genes in this area, so-called HLA genes, have high genetic variability. As Lenz puts it, these classical HLA genes are scattered across the MHC region and exhibit exceptional allelic polymorphism and an extreme level of heterozygosity, which is thought to increase pathogen resistance and thus to be maintained by pathogen-mediated balancing selection. In other words it gives our immune systems the flexibility they need to counteract the multiple and constantly evolving threats from infectious microorganisms.
However, the downside to all this is that the MHC is enriched with a number of non-HLA genes that are known to be associated with diseases like autoimmune disease, cancer and schizophrenia. These can also persist at high frequency because they lie at such close proximity to the maintained HLA variants they too are maintained by genetic linkage. Lenz noted that non-HLA genes in very close proximity had a frequency more than two orders of magnitude that of non-HLA genes a little further away. Thus, even if some of these genes have a negative effect on human fitness we cannot get rid of them – they endure because they hang on to the coat-tails of genes that are essential, and have been essential through thousands of years, for human survival.
Something a little light-hearted for a change. Hui Liu, Linda J. Waite, Shannon Shen and Donna H. Wang have just published a report on the effect of regular and enjoyable sex in later life, in the Journal of Health and Social Behaviour. It appears that, for men, having a good and lusty sex life from your mid-50s onwards carries an increased risk of later heart attacks and other cardiovascular problems. While for older women, good sex seems to be beneficial and can lead to a reduction in hypertension. The risk for sexually-active older men was twice that for men who were sexually inactive. The results of their studies are published in a popular format in Medical Express who quote one of the study’s authors saying that they are not quite sure what causes this elevated risk. It might be the extra and prolonged exertion older men have to apply to the job of reaching orgasm, it might be the medication they take to enable them to perform in the first place, or it may be that elevated testosterone levels in sexually-active older men have a deleterious effect on the health of their hearts!
Nearly 10% of the genome of all mammals is made up of viruses that infected mammalian ancestors eons ago. These retroviruses inserted their DNA into mammalian chromosomes and, while time has reduced many of them to useless genetic rubble, some of them, or fragments from them, became adopted by mammalian DNA and pressed into service by evolution.
As Carl Zimmer documented back in 2012, in a wonderful essay on “The Loom” titled “Mammals Made from Viruses”, we humans could not have been born without them. He was referring to proteins called syncytins that are produced by the ex-viral genes syncytin 1 and 2. When the placenta is developing – thrusting itself deep into the wall of the uterus – the boundary between placenta and uterus, which is essential for the transfer of nutrients from the mother to the fetus, is composed of a layer of fused cells called the syncytiotrophoblast. It is the protein syncytin that causes the cells to fuse together.
According to the French scientist, Thierry Heidmann, who has done most of the work on syncytins, there is a protein that was once part of the envelope of the retrovirus, that has immunosuppressive qualities. This would have allowed the virus to invade mammalian genomes without being destroyed by host immune systems. This immunosuppressive function has been conserved by modern syncytins, says Heidmann, and could well be a part of the crucial system of maternal immune tolerance to the combined unit of fetus and placenta, which would otherwise lead to females rejecting their own fetuses on the basis of the allogeneic effect of the paternal genes they contain.
Now Heidmann has come up with another jaw-dropping role for syncytin. In the same way that it allows cells to fuse together to form the syncytiotrophoblast, he says, syncytin allows muscle cells to form by fusing together the stem cells that give rise to them. Muscle fibers are complex multi-nucleate structures containing large numbers of contractile myotubes that are formed from the fusion of mononuclear myoblasts. In a paper last week in PLosGenetics Heidmann showed that when he knocked out one of the syncytin genes he produced mice with 20% less muscle mass and mean muscle fiber area – but the effect was only seen in males and reduced their muscle mass to the equivalent of the females. He also documented the same male-specificity in the extent to which syncytins help to repair muscles after cardio-toxin-induced injury.
If Heidmann’s research is borne out by further investigation it will mean that not only has this viral gene been turned into a gene that is vital for reproduction throughout the mammals – including us – but has a more wide-ranging pleiotropic effect in that it also contributes towards the sexual dimorphism we see throughout the mammals where males are invariably bigger and bulkier than females. An extraordinary evolutionary story.